Abstract

Background

Afatinib, an oral, irreversible ErbB family blocker, improved progression-free survival (PFS), objective response rate and symptom control in patients with EGFR mutation-positive locally advanced or metastatic NSCLC, when compared with standard platinum-doublet chemotherapy in the first-line setting. Afatinib also significantly prolonged overall survival in patients with Del19 mutations. Some EGFR mutation-positive patients still receive first-line chemotherapy and there are limited data regarding the effect of afatinib in this patient population. This study was designed to evaluate the efficacy and safety of 40 mg/day afatinib in the second-line setting.

Trial design

This is an ongoing, single-arm, open-label, Phase IV trial to enroll 60 patients with locally advanced or metastatic adenocarcinoma of the lung (stage IIIB/IV) harboring EGFR mutations who have failed first-line platinum-based chemotherapy. Inclusion criteria include age ≥18 years, ECOG PS 0 or 1, and documented EGFR Del19 and/or L858R mutation. Patients previously treated with any EGFR-targeted tyrosine kinase inhibitor or antibody are excluded. Patients from centers across Europe, Asia and North Africa will receive oral afatinib 40 mg/day until the development of progressive disease. The primary endpoint is objective tumor response (complete response [CR], partial response [PR]) according to RECIST v1.1. Secondary endpoints include PFS, disease control (CR, PR, stable disease) and assessment of safety. All patients who received at least one dose of afatinib will be included in the safety analysis. Efficacy and safety will be evaluated in a descriptive manner; there are no formal statistical hypotheses. This trial was initiated in October 2014 and is open for accrual. Study locations include 22 trial sites in 7 countries. Trial sites are currently open to enrollment in Egypt, Romania, Serbia, Malaysia, the Philippines, Poland, and Thailand. The estimated completion date for the primary outcome is December 2016; further details are at ClinicalTrials.gov (NCT02208843).